chrX-120159371-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_032498.3(RHOXF2):​c.436C>G​(p.Leu146Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000070 ( 0 hom., 0 hem., cov: 19)
Exomes 𝑓: 0.000014 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control

Consequence

RHOXF2
NM_032498.3 missense

Scores

6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.49
Variant links:
Genes affected
RHOXF2 (HGNC:30011): (Rhox homeobox family member 2) This gene, which encodes a transcriptional repressor, is one of two paralogous X-linked homeobox-containing genes and is highly expressed in a variety of cancers. In addition, the encoded protein associates with the cell membrane and with microtubules, and is concentrated at the leading edge of migratory cells. [provided by RefSeq, Dec 2015]
RHOXF1 (HGNC:29993): (Rhox homeobox family member 1) This gene is a member of the PEPP subfamily of paired-like homoebox genes. The gene may be regulated by androgens and epigenetic mechanisms. The encoded nuclear protein is likely a transcription factor that may play a role in human reproduction. [provided by RefSeq, Dec 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.14005908).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RHOXF2NM_032498.3 linkc.436C>G p.Leu146Val missense_variant Exon 2 of 4 ENST00000371388.5 NP_115887.1 Q9BQY4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RHOXF2ENST00000371388.5 linkc.436C>G p.Leu146Val missense_variant Exon 2 of 4 1 NM_032498.3 ENSP00000360441.3 Q9BQY4

Frequencies

GnomAD3 genomes
AF:
0.0000705
AC:
8
AN:
113451
Hom.:
0
Cov.:
19
AF XY:
0.00
AC XY:
0
AN XY:
35573
show subpopulations
Gnomad AFR
AF:
0.000256
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000167
AC:
3
AN:
180073
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
66111
show subpopulations
Gnomad AFR exome
AF:
0.000230
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000137
AC:
15
AN:
1096381
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
361911
show subpopulations
Gnomad4 AFR exome
AF:
0.000266
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000476
Gnomad4 OTH exome
AF:
0.0000869
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000705
AC:
8
AN:
113503
Hom.:
0
Cov.:
19
AF XY:
0.00
AC XY:
0
AN XY:
35635
show subpopulations
Gnomad4 AFR
AF:
0.000255
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000960
Hom.:
0
ExAC
AF:
0.0000495
AC:
6

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 04, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.436C>G (p.L146V) alteration is located in exon 2 (coding exon 2) of the RHOXF2 gene. This alteration results from a C to G substitution at nucleotide position 436, causing the leucine (L) at amino acid position 146 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
0.15
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.67
D
FATHMM_MKL
Benign
0.015
N
LIST_S2
Benign
0.76
T
M_CAP
Benign
0.0067
T
MetaRNN
Benign
0.14
T
MetaSVM
Uncertain
0.16
D
MutationAssessor
Benign
1.4
L
PrimateAI
Benign
0.47
T
PROVEAN
Uncertain
-2.4
N
REVEL
Uncertain
0.35
Sift
Uncertain
0.0080
D
Sift4G
Benign
0.13
T
Polyphen
0.56
P
Vest4
0.17
MutPred
0.69
Gain of catalytic residue at L146 (P = 0.071);
MVP
0.12
MPC
2.1
ClinPred
0.080
T
GERP RS
-3.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.12
gMVP
0.092

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs782288176; hg19: chrX-119293277; API